rs11654482

Variant names:

• chr17-17713773-G-A
• rs11654482
• NM_030665.4:c.-148-10255G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030665.4(RAI1):​c.-148-10255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 152,238 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.069 (454 hom., cov: 32)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.737
• Publications: 2 publications found

Genes affected

RAI1 (HGNC:9834): (retinoic acid induced 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It is highly similar to its mouse counterpart and is expressed at high levels mainly in neuronal tissues. The protein encoded by this gene includes a polymorphic polyglutamine tract in the N-terminal domain. Expression of the mouse counterpart in neurons is induced by retinoic acid. This gene is associated with both the severity of the phenotype and the response to medication in schizophrenic patients. [provided by RefSeq, Jul 2008]

RAI1 Gene-Disease associations (from GenCC):

• Smith-Magenis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Potocki-Lupski syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

LOC124903943 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-148-10255G>A		intron_variant	Intron 1 of 5	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.-148-10255G>A		intron_variant	Intron 1 of 5	1	NM_030665.4	ENSP00000323074.4
RAI1	ENST00000471135.2	c.-148-10255G>A		intron_variant	Intron 2 of 3	3		ENSP00000463607.1

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10442 AN: 152120 Hom.: 449 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0687 AC: 10463 AN: 152238 Hom.: 454 Cov.: 32 AF XY: 0.0677 AC XY: 5044 AN XY: 74458

African (AFR) AF: 0.106 AC: 4410 AN: 41536

American (AMR) AF: 0.0402 AC: 615 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5188

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4820

European-Finnish (FIN) AF: 0.0824 AC: 873 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0616 AC: 4187 AN: 68010

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.0659 Hom.: 585

Bravo AF: 0.0680

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.25
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11654482; hg19: chr17-17617087;